Insulin action on astrocytes: From energy homeostasis to behaviour

Abstract

Astrocytes are specialised glial cells that integrate distinct inputs arising from neurones, other glial cells and the microcirculation to regulate diverse aspects of brain function. A growing body of emerging evidence supports that astrocytes, similar to neurones, also play active roles in the neuroendocrine control of metabolism by responding to afferent nutritional and hormonal cues and translating these metabolic cues into neuronal inputs. Specifically, insulin action in astrocytes has received special emphasis given its newly discovered regulatory role in brain glucose uptake, which until recently was assumed to be an insulin independent process. We now know that insulin signalling in astrocytes regulates metabolic processes and behavioural responses through coupling brain glucose uptake with nutrient availability to maintain energy balance and systemic glucose homeostasis. Moreover, genetic ablation of the insulin receptor in astrocytes is associated with anxiety- and depressive-like behaviours, confirming that these glial cells are involved in the regulation of cognition and mood via insulin action. Here, we provide a comprehensive review of the most relevant findings that have been made over the course of the last few years linking insulin signalling in astrocytes with the pathogenesis of brain metabolic and neurodegenerative diseases; a still unexplored field, but with a high translational potential for developing therapies.

Keywords: astrocytes; central nervous system; cognition; food intake; glucose homeostasis; insulin.